The earlier notion that MALP-2 or any other
bacterial toll-like receptor agonists just lead to activation
of NF-kappa B as the one and only transcription factor which
initiates gene transcription is certainly oversimplified.
On the other hand, reports appear almost daily dealing with
much more complicated signal transduction pathways of toll-like
receptor agonists. It has now become clear that not all toll-like
receptor agonists signal in identical ways, nor are all toll-like
receptors exposed on the cell surface. The pathway indicated
below is but a model of how MALP-2 could
It is based on data from my own lab as well as on those from
many colleagues around the world. The advantage of such cartoons
is that they simplify very complex events and that they help
to connect and put into perspective seemingly independent
observations. One problem with such models is that they necessarily
rely on sometimes conflicting reports. Other problems arise
from interpreting ones own results and those of others.
Questions arise such as, is the agonist really pure or are
we possibly looking at effects of biologically active contaminants?
Or else, are we looking at a primary effect of the agonist
in question or do we see secondary, autocrine or paracrine
effects arising from early released cytokines acting back
on the system under observation? The model below ought thus
to be regarded with the necessary scepticism. It is almost
certain that it needs modifications and occasional updates.
Note: the reason why some target genes appear downstream
of different sub-pathways results from the fact that genes
require several different transcription factors in order to
become activated. Note that some transcription factors are
listed as such, but additionally as target (e. g. immediate